ischemic and toxic renal injury and renal disease in pregnancy
TRANSCRIPT
Ischemic and toxic renal injury and Renal disease in pregnancy
Presentor : Dr. Pallavi PrasadModerator : Dr. Manoj Jain
Acute Renal Failure/Acute Tubular Injury
Pathology of Acute Renal Failure/Acute Tubular Injury
• Enlarged and swollen kidneys• On cut section, the tissue bulges above the cut surface and
has a flabby consistency. • The cortex is widened and pale. • The outer medulla may appear as a deep red band
Histopathology of Acute Tubular Injury
• Glomeruli – spared• Glomeruli- ischemic collapse• Bowman's space - dilated
“Tubularization” of parietal epithelial cells
Histopathology of Acute Tubular Injury
postischemic ATI nephrotoxic ATI
The sites of tubular damage along the nephron differ between the two forms
Ischemic Acute Tubular Injury
Early : minimal alterations to severe cell swelling to individual cell necrosis with denudation of the basement membrane
Shedding of both viable and necrotic epithelial cells into the tubular lumen.
Brush border of proximal tubules is thinned or absent. Blebs of apical membrane and intact cells Individual cell necrosis Hyaline, granular, cellular, and/or pigmented casts are seen in
the distal portions of the nephron and in the collecting ducts
Tubular cells showing severe cell swelling
single tubular cell loss
Detached necrotic tubular cells Granular casts with necrotic cell debris
Apical blebbing
Intact tubular cells in the urine
Intact exfoliated tubular cells in tubular lumen
Tubular cell casts in collecting ducts in papilla
Nephrotoxic Acute Tubular Injury
• Extensive epithelial necrosis• Involves nephrons more uniformly than in the ischemic form
Nephrotoxic Acute Tubular Injury : LM features
• Alterations in the surface of the cells (loss of brush border (detectable on PAS), loss of basolateral infoldings, and blebbing of apical cytoplasm)
• Cytoplasmic swelling and vacuolation• Intracellular inclusions• Extensive tubular cell necrosis• Loss of individual tubular cells• Intraluminal proteinaceous cellular debris, casts, or crystals• Tubular dilatation with flattening of tubular epithelium• Tubular rupture with urinary extravasation• Regenerative changes
Severe cell swelling with IvIg
Isometric vacuolization
• Tubular simplification • The denuded basement membrane gaps are covered by
spreading of adjacent viable epithelial cells
regenerative changes
Ki-67
Erythrocyte congestion and nucleated cells in dilated vasa recta in outer medulla
Coagulative necrosis, with cell debris in tubular lumina
Oxalate crystals in allograft kidney
Pathology of Specific NephrotoxinsNephrotoxin Findings
Amphotericin Calcification of tubules
Anaesthetic agents, antiretroviral, sulphonamides, radiocontrast agents
crystals
Cocaine Pigmented casts
Antiretroviral agents Crystalsgranulomas
Aminoglycosides ATI, TIN
Cyclosporine Intratubular calcificationNodular hyalinosis of blood vessels
Calcification of tubular cells [amphotericin]Striking vacuolization of smooth muscle cells
Crystalline precipitates [intravenous acyclovir]
Indinavir crystal
Pigmented casts [cocaine]
Thrombotic microangiopathy [tacrolimus]
Renal disease in pregnancy
Urinary tract infections
Hypertensive Disorders of Pregnancy
HELLP Syndrome
Acute Renal Failure in Pregnancy
Pregnancy and Pre-Existing Renal Disease
I) Renal Infection in Pregnancy• In infected emboli• In pregnancy, retrograde spread from an infected focus lower
down the urinary tract• Impaired contractility of the ureter• Mechanical obstruction by a gravid uterus in women when
standing
multiplication and spread of bacteria
Renal Infection in Pregnancy
• Pyelitis or pyelonephritis• Asymptomatic bacteriuria
• Symptomatic infections during pregnancy• Bacteriuria has no established histopathological basis
II) Hypertensive disorders of pregnancy
Chronic hypertension
Chronic hypertension with superimposed preeclampsia
Late/transient hypertension
Preeclampsia and eclampsia
Hypertensive disorders of pregnancy
1) Chronic hypertension : Renal insufficiency developed in 4% of
non-proteinuric pts (24% of proteinuric pts) Fibromuscular
dysplasia- young females
2) Chronic hypertension with superimposed preeclampsia
3) Late/transient hypertension
4) Preeclampsia and eclampsia :
GFR reduced..
Preeclampsia and Eclampsia
• Nephrosclerosis = 74% of patients had hypertension on follow-up.
• 9.4% of preeclamptic patients without vascular lesions developed hypertension.
Hyperuricemia, Na retention,
FDPs, fibronectin- raised
Platelet counts – reduced
Urine : RBCs, WBCs, casts
Pathogenesis for preeclampsia
Gross appearance
• No distinctive changes visible to the naked eye • Normal size /slightly enlarged• Cortex is pale and widened in the larger kidneys• Glomeruli - unduly prominent
Microscopic findings in preeclampsia and eclampsia
• Glomeruli : enlarged and swollen, bloodless • Lobular pattern from capillary expansion producing cigar-
shaped lobules. • Glomerular capillary lumina are narrowed /obstructed b/o
mesangial and endothelial cell swelling and hypertrophy= glomerular capillary endotheliosis
Microscopic findings in preeclampsia and eclampsia
• Endotheliosis-like lesions :• Pathognomonic for preeclampsia• Normotensive patients with abruptio placentae • Normal pregnancy
glomerular capillary loops are ballooned at the tubular pole
herniation of the glomerular tuft into the proximal tubule pouting
bubbly appearance in the consolidated areas
segmental hyaline droplets in the podocytes
glomerular basement membrane splitting
endotheliosis lesion and segmental early TMA
endotheliosis lesion and extensive severe TMA
fibrinoid necrosis Intraluminal fibrin
double contours of the GBM segmental sclerosis and hyalinosis
intraluminal fibrin and early intimal proliferation
Frequency and course of glomerular lesions associated with preeclampsia
Lesion Frequency Course
Endotheliosis Invariable Reversible over weeks to months
Foam cells Rare peripartum, more frequent postpartum
Resolve
Subendothelial deposits Frequent peripartum Electron microscopic deposits resolve over first week, Ig staining resolves over 2-3 months
Glomerular basement membrane reduplication
severe disease Usually resolves rapidly, may persist for months
Fibrin or related products Rare by light microscopy; frequent by EM and IF
Resolution over weeks
Focal segmental glomerulosclerosis
Variable Not clinically progressive
Microscopic findings in preeclampsia and eclampsia
• Tubulointerstitium : IFTA, resorption droplets, casts• Blood vessels :a) Medial hypertrophy of arteriesb) Hyalinosisc) Arterio and arteriolosclerosis
Electron microscopy
• Swelling of endothelial and mesangial cells• lysosomes• Mesangial cell interposition• Vacuolisation, droplets, dense bodies, cytoplasmic strands• Glomerular epithelial cells vacuolisation & swelling• Increased lucency of lamina rara interna
Double contour of GBM
Electron micrograph from a 19-year-old woman with eclampsia
prominent mesangium
intracapillary cell with numerous empty spaces
Marked increased lamina rara interna
Lucent expanded subendothelial zone with scattered granular material
III) HELLP syndrome
Develops rapidly Benign to catastrophic
Marked coagulation abnormalities
HemolysisLFT abnormalities
ATN (31)Cortical necrosis (1)
IV) Acute Renal Failure in Pregnancy
Acute pyelonephritis Preeclampsia, eclampsia, and HELLP syndrome Uterine hemorrhage Septic abortion Cortical necrosis Acute fatty liver of pregnancy Postpartum hemolytic uremic syndrome
Renal Cortical Necrosis• Classic coagulative necrosis• Marked congestion• Tubular and glomerular architecture is preserved but gradual
loss of viable cytologic structure occurs. • The cytoplasm becomes homogeneous and eosinophilic, and
the nuclei demonstrate condensation and karyorrhexis
Renal Cortical Necrosis
• Polymorphonuclear leukocytic infiltration• As the lesion progresses, the central necrotic area becomes
smaller, and organization around the periphery• Eventual collapse of the central necrotic area and
replacement by collagenous scarring
Sheehan and Moore in 1952 :
Focal
Minor
Patchy
Scattered ~ 5mm
2-3 mm lesions mainly in the outer cortex
2/3rds of cortical tissue
IV) Acute Renal Failure in Pregnancy
Acute Fatty Liver of Pregnancy Fatty vacuolization in renal tubulesTubular regeneration or focal necrosisIntraglomerular thrombi- reported rarely
Septic shock transient decrease in the GFR
Uterine Hemorrhage abruptio placentae, DIC
Postpartum HUS
Postpartum Hemolytic Uremic Syndrome
schistocytes
Postpartum HUS
Fibrin thrombiSegmental hyalinosis
Tubular regeneration
Cortical necrosis
intimal fibrosismedial
hypertrophy TMA-like lesions
EclampsiaPreeclampsia
Specific Renal Diseases and Pregnancy
Antiphospholipid antibodies
• Increase in prevalence in patients with SLE during pregnancy ; poor outcome.
Vascular thrombosis
Decreased renal function
Hemolytic anemiaThrombocytopeni
a
Decidual vasculopathy
Antiphospholipid antibodies
• Acute fibrinoid lesions with fibrin thrombi in glomeruli, arterioles, and arteries
• Double contours of capillary walls• Recanalizing thrombi and cellular intimal proliferation• Vasculitis involving medium- sized and smaller arteries
• IgA Nephropathy• Mesangial (non-IgA) glomerulonephritis was associated with
the best prognosis• DPGN with advanced tubular atrophy, interstitial fibrosis, and
arteriosclerosis• Superimposed focal and segmental hyalinosis and sclerosis or
diffuse mesangial proliferation poor prognosis• Membranous Glomerulonephritis• Favorable renal prognosis • Nephrotic-range proteinuria poor fetal outcome
Systemic and Genetic Diseases
Diabetes Mellitus Increased proteinuria and serum creatinine
Anti-Glomerular Basement Membrane Antibody Disease
Pregnancy ameliorates the activity of antibodies
Kidney Transplant no adverse long-term effect on renal allograft function or survival was detected
Renal Cancer incidental detection during pregnancy because of the routine use of ultrasound
Case-1
• 24y/F• Non diabetic / non hypertensive• Post partum acute kidney injury• Decreased urine output, high grade fever, breathlessness,
nausea• Advanced renal failure , received 4 sessions of hemodialysis
outside• ? TMA/ renal biopsy proven acute cortical necrosis
Acute cortical necrosis
Case-2
• 29y/F• Non diabetic / non hypertensive• Abdominal pain / vomiting ( 1-2 episodes ), diarrhoea ( 8 -10
episodes), decreased urine output, edema• Found to have moderate renal failure / given 3 sessions of HD
outside • Referred to SGPGIMS for further management
• Lab investigations:• S creatinine : 3.3 mg/dl• TLC = 7.5• Platelet count = 298• Reti count = 2%• PBS : anisocytosis, schistocytes+• Antids-DNA, ANA = negative
• ?HUS/TTP
TMA with ATN
Case-3
• 31y/F• Non- diabetic, non- hypertensive• Underwent LSCS • C/o reduced urine output and passing pinkinsh urine 3- 4 days
after delivery, loose stools for 1 day, progressive edema of limbs
• On evaluation outside, AKI, anemia and reduced platelet count
• HD done outside but due to non- recovering renal functions patient was referred to SGPGIMS
• Lab investigations:• S creatinine : 4.2 mg/dl• TLC = 4.4• Platelet count = 177• Reti count = 2.6 %• PBS : Normocytic normochromic• ANCA negative• ANA = 2+ at 1:80• Urine = 25-30 RBCs/hpf
• ?TMA/ Acute cortical necrosis due to PPH
Patchy cortical necrosis with TMA and ATN